West Nile Virus Capsid Protein Interacts With Biologically Relevant Host Lipid Systems

Autor: Nuno C. Santos, Ana S. Martins, Ivo C. Martins, Filomena A. Carvalho, André F. Faustino
Přispěvatelé: Repositório da Universidade de Lisboa
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Microbiology (medical)
viruses
lipid droplets
Lipoproteins
030106 microbiology
Immunology
lcsh:QR1-502
Sequence (biology)
ComputingMilieux_LEGALASPECTSOFCOMPUTING
force spectroscopy
Dengue virus
Lipoproteins
VLDL
medicine.disease_cause
Microbiology
lcsh:Microbiology
Cell Line
03 medical and health sciences
zeta potential
Atomic force microscopy
Cellular and Infection Microbiology
Lipid droplet
Cricetinae
medicine
Animals
Humans
Original Research
atomic force microscopy
Chemistry
Force spectroscopy
dynamic light scattering
Zeta potential
Lipid Metabolism
Lipid droplets
3. Good health
lipoproteins
030104 developmental biology
Infectious Diseases
Capsid
Interaction with host
Ionic strength
Host-Pathogen Interactions
Biophysics
Dynamic light scattering
Capsid Proteins
West Nile virus
Intracellular
Protein Binding
Zdroj: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Frontiers in Cellular and Infection Microbiology
Frontiers in Cellular and Infection Microbiology, Vol 9 (2019)
ISSN: 2235-2988
DOI: 10.3389/fcimb.2019.00008
Popis: Copyright © 2019 Martins, Carvalho, Faustino, Martins and Santos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
West Nile and dengue viruses are closely related flaviviruses, originating mosquito-borne viral infections for which there are no effective and specific treatments. Their capsid proteins sequence and structure are particularly similar, forming highly superimposable α-helical homodimers. Measuring protein-ligand interactions at the single-molecule level yields detailed information of biological and biomedical relevance. In this work, such an approach was successfully applied on the characterization of the West Nile virus capsid protein interaction with host lipid systems, namely intracellular lipid droplets (an essential step for dengue virus replication) and blood plasma lipoproteins. Dynamic light scattering measurements show that West Nile virus capsid protein binds very low-density lipoproteins, but not low-density lipoproteins, and this interaction is dependent of potassium ions. Zeta potential experiments show that the interaction with lipid droplets is also dependent of potassium ions as well as surface proteins. The forces involved on the binding of the capsid protein with lipid droplets and lipoproteins were determined using atomic force microscopy-based force spectroscopy, proving that these interactions are K+-dependent rather than a general dependence of ionic strength. The capsid protein interaction with host lipid systems may be targeted in future therapeutic strategies against different flaviviruses. The biophysical and nanotechnology approaches employed in this study may be applied to characterize the interactions of other important proteins from different viruses, in order to understand their life cycles, as well as to find new strategies to inhibit them.
This work was supported by Fundação para a Ciência e a Tecnologia–Ministério da Ciência, Tecnologia e Ensino Superior (FCT-MCTES, Portugal) project PTDC/SAUENB/117013/2010. AF and AM also acknowledge FCT-MCTES fellowships SFRH/BD/77609/2011 and PD/BD/113698/2015, respectively. IM acknowledges consecutive funding from the FCT-MCTES fellowship SFRH/BPD/74287/2010 and the Program Investigador FCT (Research Contract IF/00772/2013). This work was also supported by UID/BIM/50005/2019, project funded by FCT-MCTES through Fundos do Orçamento do Estado.
Databáze: OpenAIRE
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